232622017-09-16Probabilistic Analysis of Renal Stones in US Astronauts (PI=Kassemi)CompletedJan 2011May 2015A combined transport-kinetics model for nucleation, growth, and agglomeration of calcium oxalate crystals was developed in the framework of the population balance equation whereupon the nephron was treated as a continuous crystallizer. The model was used to investigate the growth rates and size distributions of renal calculi based on parametric simulation case studies for normal and stone-forming subjects in 1g and microgravity. To investigate the transport effects of gravity on the formation and development of renal calculi in the nephron, the Population Balance Equation (PBE)-agglomeration model was further incorporated into the multipurpose computational fluid dynamics (CFD) code Ansys-Fluent and coupled to the Navier-Stokes and species equations that describe the urinary flow and transport of calcium and oxalate ions through the nephron. Numerical results indicate that the typical renal biochemistry of normal subjects on Earth as exemplified by low urinary calcium and oxalate concentrations, higher relative velocities between urinary flow and the calculi, and lower reaction rates due to presence of normal concentration of inhibitors will lead to surface reaction limited crystal growth rates. However, in microgravity, due to the possibility of increased supersaturation levels arising from lower urine volumes and higher calcium and oxalate concentrations, a negligible relative velocity between the stone and the urinary flow, and the lower inhibitor concentrations, the stone growth will be limited by the transport of ions in the bulk liquid. The numerical simulations further indicate that: 1. The distribution of stone sizes and their respective population densities are both quite sensitive to the different biochemistries of normal and stone-forming subjects in 1g and microgravity. 2. Stone formers exhibit parabolic distributions with peak of stone populations shifting from 2 microns in 1g to about 5-7 microns in reduced-gravity and when precipitation is the main mechanism for growth. 3. Normal subjects exhibit a monotonic decrease in precipitating stone size populations from seed size to about 8 microns in microgravity. 4. As a result of the shift in the renal biochemistry upon exposure to microgravity, a normal subject in space can exhibit stone growth rates and size distributions that are comparable to a stone-former on Earth -- a finding that may prove important to the astronaut screening protocols. 5. Agglomeration is likely to be the most important and critical mechanism in development and enlargement of renal stones causing around ten-fold increase in the resulting stone sizes. 6. Stone size distribution is quite sensitive to the magnitude of the agglomeration coefficient – a quantity that unfortunately may vary substantially for different urine biochemistries and therefore not well-quantified in published literature. 7. The gravitational field plays an adverse effect increasing the transit time of renal calculi in the nephron with a possibility of a nearly two-fold stone size enhancement. In summary, the results so far imply that while a typical stone-former may form considerably larger renal stones on Earth, the normal subject in microgravity tends to make significantly more stones below the 2 micron range by nucleation and precipitation. Agglomeration of these crystals in the nephron may result in a 10 fold further increase in the stone sizes in microgravity. The stones in this size range will still clear through the nephron. But unfortunately, upon re-entry into a gravitational field, further growth and agglomeration of the renal calculi combined with increased transit times due to the lagging of the stones behind the urinary flow in tubule sections where gravitational vector is acting in the adverse direction can result in size increases alarmingly close to the critical dimension for retention. In this case, the risk for a clinical stone occurrence may be greatly enhanced. The development of the Renal Stone Formation Simulation Module (RSFSM) and its validation has been nearly completed in 2013. In the final year of the project (2014), this model will be used to perform a series of comprehensive parametric simulation case studies to investigate effect of hydration and inhibition. Furthermore, the core deterministic PBE model will be coupled to front and back end probabilistic wrapper models. Simulations performed using the combined deterministic-probabilistic model will be used to provide a probabilistic assessment of the risks of clinical stone incidents for future space mission scenarios.Nephrolithiasis constitutes as one of the most common diseases that has afflicted man for centuries. Indeed, one of the first evidences of renal stones in humans was found in an Egyptian mummy at El- Amrah dating back to 4800 B.C. Today, approximately 5% of the U.S. population develops clinically significant urinary calculi in their lifetime. However, renal stone disease is not only a concern on Earth, but could conceivably pose as a serious risk to the astronauts’ health and safety in space. The physiological, environmental, and dietary conditions imposed by space travel and weightlessness can easily increase this risk as a recent survey of renal stone formation in U.S. astronauts has revealed 14 recorded episodes. Russian medical science investigators have also noted multiple stone events among the Soviet cosmonauts. The most serious one was an in-flight renal stone occurrence that nearly caused the abortion of the Russian mission. The Renal Stone Formation Simulation Module (RSFSM) developed as part of this task is designed to inform NASA's Integrated Medical Model (IMM) with the likelihood and associated uncertainty of astronauts developing kidney stones upon long-term exposure to microgravity, as well as upon re-entry to a gravitational field. The computational module will be able to assess the effects of various design reference mission scenarios, thus allow mission planners, medical kit designers, and clinicians to compare the efficacy of various countermeasures devised to reduce the probability of developing renal stone incident during the mission. The understanding that these simulations provide will also help to improve the astronauts' screening protocols. The benefits of developing this computational capability are not limited to space applications but will extend back to impact clinical and scientific medicine on Earth. As a state-of-the-art research tool and virtual hypothesis-tester, RSFSM will expand the current level of understanding of renal stone disease. It will also serve as a tool to help improve clinical procedures for screening and treating nephrolithiasis on Earth and devise physical and/or pharmaceutical interventions to help the nearly 15 million Americans who currently suffer from this ailment today.32446Human Health, Life Support, and Habitation Systems32906.3Human Health and Performance37266.3.1Medical Diagnosis and PrognosisHuman Research ProgramHuman Exploration and Operations Mission DirectorateJohnson Space CenterJSCNASA CenterHoustonTXGlenn Research CenterGRCNASA CenterClevelandOHNational Center for Space Exploration ResearchNCSERU.S. GovernmentOhioWilliam PaloskiSharmila WatkinsMohammad KassemiJerry Myershttp://humanresearchroadmap.nasa.gov/tasks/task.aspx?i=110925510Abstracts for Journals and ProceedingsStoryKassemi M, Iskovits I, Brock R. "A Combined Transport-Kinetics Model for Growth of Renal Calculi in 1G and Microgravity." 2012 NASA Human Research Program Investigators’ Workshop, Houston, TX, February 14-16, 2012. 2012 NASA Human Research Program Investigators’ Workshop, Houston, TX, February 14-16, 2012. <a target="_blank" href="http://www.dsls.usra.edu/meetings/hrp2012/pdf/4040.pdf">http://www.dsls.usra.edu/meetings/hrp2012/pdf/4040.pdf</a> , Feb-201226089Abstracts for Journals and ProceedingsStoryKassemi M, Iskovitz I. "Renal Stone Formation Module (RSFM): Predicting Renal Stone Size Distribution in Microgravity Using a Population Balance Approach." 2013 NASA Human Research Program Investigators’ Workshop, Galveston, TX, February 12-14, 2013. 2013 NASA Human Research Program Investigators’ Workshop, Galveston, TX, February 12-14, 2013., Feb-201325018Articles in Peer-reviewed JournalsStoryKassemi M, Brock R, Nemeth N. "A combined transport-kinetics model for the growth of renal calculi." Journal of Crystal Growth. 2011 Oct;332(1):48-57. <a target="_blank" href="http://dx.doi.org/10.1016/j.jcrysgro.2011.07.009,">http://dx.doi.org/10.1016/j.jcrysgro.2011.07.009,</a> Oct-201125812Papers from Meeting ProceedingsStoryKassemi M, Iskovitz I. "Prediction of Renal Stone Development and Size Distribution in Microgravity Using Population Balance Equation." 43rd International Conference on Environmental Systems, Vail, CO, July 14-18, 2013. To be presented in Computational Modeling for Human Health and Performance Analysis session. 43rd International Conference on Environmental Systems, Vail, CO, July 14-18, 2013. Paper 1574858, Session: ICES513, Computational Modeling for Human Health and Performance Analysis., Jul-201325861Papers from Meeting ProceedingsStoryKassemi M, Iskovitz I. "Role of Transport and Kinetics in Growth of Renal Stones." 42nd International Conference on Environmental Systems, San Diego, CA, July 15-19, 2012. Paper AIAA-2012-3449. 42nd International Conference on Environmental Systems, San Diego, CA, July 15-19, 2012. <a target="_blank" href="http://dx.doi.org/10.2514/6.2012-3449">http://dx.doi.org/10.2514/6.2012-3449</a> , Jul-20128596Papers from Meeting ProceedingsStoryKassemi M, Iskovitz I. "Prediction of Renal Stone Development and Size Distribution in Microgravity Using Population Balance Equation." Paper AIAA-1574858, Session: ICES513, Computational Modeling for Human Health and Performance Analysis, presented at 43rd AIAA International Conference on Environmental Systems, Vail, CO, July 14-18, 2013. Paper AIAA-1574858. 43rd AIAA International Conference on Environmental Systems, Vail, CO, July 14-18, 2013. <a target="_blank" href="http://dx.doi.org/10.2514/6.2013-3319">http://dx.doi.org/10.2514/6.2013-3319</a> , Jul-2013